Desensitizing dental composition

ABSTRACT

A dental desensitizing two-phase composition wherein one phase contains physiologically acceptable strontium ion and the second phase contains physiologically acceptable fluoride ion. The two phases are mixed when used.

BACKGROUND OF THE INVENTION

This invention relates to a desensitizing dental composition and moreparticularly to a two-component desensitizing dental composition.

Hypersensitivity is a common phenomenon among dental patients that oftencauses the patient to reject dental treatment. The sensitivity may belocal or general and very often complicates treatment of a variety ofdental problems. Treatment of hypersensitivity has resulted in varyingdegrees of success. These treatments often have relied upon astringentor coagulating effects of various agents, occulating properties or theability to render calcium less soluble. Examples of these agents includefluoride, formaldehyde, silver nitrate, zinc oxide and strontiumchloride.

Strontium chloride has been shown to be particularly effective in itsdesensitizing effect. However, strontium chloride is highly soluble inaqueous solution so that when presented to the teeth as an aqueoussolution, it is not particularly effective since it has a higheraffinity for water rather than the surface of the teeth. In order to beeffective, the strontium must penetrate the tooth surface. It has alsobeen proposed to combine strontium chloride with a physiologicallyacceptable source of fluoride since the fluoride has been shown to beeffective in preventing or minimizing cavity formation in teeth.However, attempts to form mixtures including a source of strontium and asource of fluoride have proven ineffective as a means for deliveringboth strontium and a fluoride to the teeth since they readilyprecipitate to form strontium fluoride and, as a precipitate, areineffective to penetrate the tooth surface to provide the desired dentaleffect.

It has been proposed in Canadian Patent No. 907,514 to Stearns et al toprovide a dental desensitizing composition including a source offluoride and a source of strontium which is complexed with a chelatingagent such as ethylenediamine tetraacetic acid in order to preventprecipitation of strontium chloride so that, upon use, the fluoride andthe strontium area available separately to the tooth surface to allowpenetration into the tooth for their desired effects. However, thechelating agent to which strontium is complexed renders it much moredifficult to deposit onto the tooth surface as compared to strontium ionper se. The chelating agent greatly inhibits the insitu reaction ofstrontium and fluoride which must occur on the tooth surface in order toallow deposition of both on the tooth surface, thereby to effect toothdesensitization.

Accordingly, it would be highly desirable to provide a dentaldesensitizing composition which is a source of both strontium andfluoride both of which are in the form which permits ease of theirpenetration into or adherence onto the tooth in order to attain thedesired dental effect. Accordingly, it would be desirable to provide adental desensitizing composition wherein strontium fluoride formation isminimized before the time the composition is applied to the teeth andwherein the strontium ion remains uncomplexed so that it can easilypenetrate the surface of the teeth when applied directly to the teeth.

SUMMARY OF THE INVENTION

In accordance with this invention, there is provided a system forpreparing a desensitizing composition comprising strontium and fluoride,said system comprising a source of first and second compositions saidcompositions being segregated and containing respectively aphysiologically acceptable source of free strontium ions and aphysiologically acceptable source of free fluoride ions and dispensingmeans arranged to dispense said compositions so that a mixture thereofmay be formed on or immediately prior to application thereof to theteeth.

More specifically the invention provides a package is provided whichhouses a dental desensitizing composition which includes aphysiologically acceptable source of strontium ion and a physiologicallyacceptable source of fluoride ion wherein the physiologically acceptablesource of strontium ion and the physiologically acceptable source offluoride ion are maintained separate from each other and are not admixeduntil application to the teeth is desired. When admixed on the teeth,the resultant mixture contains both free strontium ion and free fluorideion.

This mixture interacts with the teeth and both components are morerapidly immobilized on the teeth surface because of the presence of bothcomponents initially in the uncomplexed free ion form.

It has been found that by operating in this manner, the compositions ofthis invention are far more effective than compositions which containstrontium ion chemically bound to a chelating agent or bound to fluoridein the form of strontium fluoride.

The package may include compartments, one for housing the strontium ionin the absence of fluoride ion and another for housing fluoride in theabsence of strontium ion. Each of the strontium and fluoride ions thencan be dispensed simultaneously on the teeth surfaces.

A method also is provided for treating a patient having a dentalhypersensitivity by depositing both ions on the teeth surfaces andmixing the ions directly on the teeth surfaces.

The invention further provides a kit for densitizing the dental area ofa patient having hypersensitive teeth which comprises supplies of twoseparate dentifrice or mouthwash compositions, one of said compositionscontaining a source of a physiologically acceptable free strontium ionand the other of said compositions containing a physiologicallyacceptable source of free fluoride ion, and optionally instructions foradmixing said phases on or immediately prior to application to the teethof the patient to form on the surface of the teeth strontium andfluoride in a form to effect desensitization of the dental area of thepatient.

The use of a physiologically acceptable source of fluoride to produceindustrially a kit or system for the treatment of teeth in a combinationtherapy involving the application of strontium ions and fluoride ionsusing separate compositions containing strontium ions and fluoride ionsforms a further aspect of the invention, as does the use of aphysiologically acceptable source of strontium to produce industrially akit or system for the treatment of teeth in a combination therapyinvolving the application of strontium ions and fluorine ions usingseparate compositions containing strontium ions and fluorine ions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional side view of a dispenser suitable for use incarrying out the present invention.

FIG. 2 is a cross-sectional view taken along line 2--2 of FIG. 1.

FIGS. 3-6 illustrate graphically the results of experiments carried outto demonstrate the efficacy of the invention.

DESCRIPTION OF SPECIFIC EMBODIMENTS

The present invention is useful in any topically applied dentaldesensitizing composition including toothpastes, mouthwashes or thelike. The physiologically acceptable source of strontium ion ismaintained in a phase of the composition separate from a phasecontaining the physiologically acceptable source of fluoride ion.

Any convenient means for effecting the separation can be utilized. Forexample, a single container can be compartmentalized so that thestrontium containing phase and the fluoride containing phase are housedin separate compartments and are not admixed until applied to the teeth.Alternatively, the strontium containing phase and the fluoridecontaining phase can be housed in separate containers from which therespective phases are dispensed for admixture just prior to use.

Thus for example, in one embodiment said segregated compositions arehoused in a common container and are separated from one another by abarrier which prevents mixing prior to the compositions being dispensed.The barrier may comprise a wall integrally formed with said container orit may comprise a physiologically acceptable composition which isadapted to be dispensed from said container with said segregatedcompositions.

Applicant's invention is based upon the discovery that when a source offluoride and a source of strontium which have been maintained separatefrom each other are combined for the first time on the surface of theteeth, a synergistic effect is obtained as a result of interaction ofstrontium and fluoride on or close to the tooth surface, leading tobetter strontium uptake by the teeth in preference to dissolution in theaqueous medium from which it is derived and before the conversion ofstrontium into less-active forms, such as strontium fluorideprecipitate, which removes both components from availability to theteeth. When both components are added simultaneously to the teeth thedesensitizing is thus enhanced. If the fluoride and the strontium wereto be applied separately, the desired synergistic effect would not occuror would occur only to an insignificant extent as a result, for example,of the natural level of the other component in saliva, the drinkingwater or on the tooth surface. Since this is typically much lower thanthe proposed levels the densitizing effect is much smaller.

When the strontium and the fluoride are housed in a manner allowingpremature admixture, undesirable precipitation of strontium fluorideoccurs so that much lower levels of the free components are availablefor adsorption by the teeth.

Furthermore, if either the strontium ion or the fluoride ion iscomplexed, the formation of the reaction product of strontium andfluoride is significantly reduced but the rate of deposition ofstrontium on the teeth is also so reduced as to adversely affect itsdensensitization property. For example, when strontium is complexed witha chelating agent such as EDTA, precipitation by fluoride is inhibited,but the strontium is also rendered very water-soluble so that is doesnot interact effectively with the teeth.

Representative suitable sources of physiologically acceptable fluorideion include sodium fluoride, potassium fluoride, lithium fluoride, zincfluoride, ammonium fluoride, rubidium fluoride, potassium bifluoride,ammonium bifluoride, sodium silicofluoride, mixtures thereof or thelike. The fluoride ion is contained in the fluoride-containing phase ata concentration between about 0.001% and about 4% preferably betweenabout 0.02% and about 2%. In order to maintain the fluoride in the formwhich permits its subsequent penetration into the tooth, the pH of thefluoride-containing composition is maintained between 3 and about 9,preferably between about 5 and about 8. It is preferred to utilizeacidified monofluorophosphate for fluoride because it is safe and easilyreleases fluoride when in an aqueous medium.

Representative suitable sources of strontium include strontium chloride,strontium nitrate, strontium acetate, strontium bromide, strontiumiodide, strontium bromate, strontium perchlorate, strontium formate,strontium lactate, mixtures thereof or the like. Thestrontium-containing phase is maintained at a pH of between about 3 andabout 7, preferably between about 5 and 7 so that the strontium ion issolubilized within the strontium ion-containing phase. The strontium ispresent in the strontium-containing phase at a concentration betweenabout 0.1% and about 12%, preferably between about 8% and 12%. Thepreferred source of strontium is strontium chloride since it is readilydissolved in an aqueous medium.

It is of course desirable that said strontium containing composition issubstantially free of free fluoride and said fluoride-containingcomposition is substantially free of free strontium.

The strontium and the fluoride are most conveniently maintained in aviscous aqueous medium such as in the form of a gel or a paste. It ismost preferred that the strontium and the fluoride be present in eithera toothpaste composition suitable for cleaning teeth, in a mouthwashwith desensitizing properties, or in a gel composition of the typecommonly employed by dentists in order to apply treatment compositionsto the teeth or gum surface. The toothpaste compositions typicallycontain water, a foaming agent such as sodium lauryl phosphate, a smallproportion of abrasive particles such as silicates, carbonate ordehydrated silica gels, flavors and sweeteners.

When it is desirable to form the strontium-containing phase and thefluoride-containing phase as a gel, an aqueous solution of the strontiumor the fluoride is admixed with a pharmaceutically acceptable gellingagent such as sodium carboxymethyl cellulose, hydroxyethyl cellulose,hydroxypropyl cellulose, magnesium aluminium silicate, silica gel or thelike. The thixotropic properties of the resultant gel can be varied byvarying the concentration of the gelling agent with increasedconcentrations providing increased thixotropic properties as is wellknown in the art. When it is desired to form the strontium-containingphase and the fluoride-containing phase as aqueous solutions as could beused as a mouthwash, separate aqueous solutions of strontium andfluoride may for example be enclosed in a two-compartment bottle fromwhich both solutions can be dispensed simultaneously immediately priorto use as a mouthwash.

The compositions utilized in the present invention are convenientlyformed by first preparing an aqueous solution of either the strontiumcompound or the fluoride compound, preferably in deionized water. Theconcentration of the strontium compound is such that in the finalcomposition it comprises between about 0.1 and about 12 weight percentof the final composition (exclusive of the fluoride-containingcomposition), preferably between about 8 and about 12 weight percent.Similarly, the fluoride-containing composition in the aqueous solutionshould be such that the concentration of the fluoride in the finalcomposition is between about 0.001 and about 4 weight percent (exclusiveof the strontium-containing phase), preferably between about 0.02 andabout 4 weight percent. After the aqueous solution has been formed, theconventional agents utilized to form a paste or a gel or the like maythen be admixed with the aqueous solution to form the final composition.

Referring to FIGS. 5 and 6, a suitable container 10 useful in thepresent invention comprises an outer wall formed of a flexible materialsuch as a polymer which can contain a sheet of flexible metal such asaluminium 12. The container 10 is segmented into two compartments 14 and16 by means of wall 18 which is sealed to the interior surface of theouter wall 12. One end 20 of the container 10 is sealed while theopposing end 22 is open so that it can be conveniently opened or closedin a conventional manner such as with a screw cap (not shown).Compartment 14 can house either the strontium phase of the fluoridephase while the other compartment 16 can house the phase not housedwithin compartment 14. It is to be understood that thestrontium-containing phase and the fluoride-containing phase can behoused in separate containers from which they can be convenientlydispensed just prior to being topically applied to the dental area ofthe user. Alternatively, an intermediate layer of toothpaste, gel or thelike containing neither strontium nor fluoride can be interposed betweenthe strontium layer and the fluoride layer with in the same container sothat mixture of the strontium layer and the fluoride layer does notoccur until use.

The following examples illustrates the present invention and are notintended to limit the same.

EXAMPLE 1 In Vivo Tests

A layer of a commercially available fluoride toothpaste and a layer of acommercially available strontium chloride containing toothpaste weredispensed simultaneously. The concentrations used were 10% SrCl₂.6H₂ Oin one toothpaste and 1.23% acidulated phosphate fluoride in the othertoothpaste.

Mixing was obtained by brushing the two layers directly on the teeth ofeach patient. Each patient was treated at the 4 quadrants of the mouth.One quadrant was treated with the layered Sr² +.2F toothpastepreparation; one quadrant was treated with a Sr² +.2F containingtoothpaste only; one quadrant was treated with the acidulated phosphatefluoride toothpaste only; while one quadrant was untreated (blank). Theprocedure was carried out daily on 12 patients for a total period of upto 6 months. All patients reported some relief in the mixture quadrant,with some reporting no relief in any quadrants. Generally, a significantimprovement over the results obtained with either one of the toothpastesused singly was reported subjectively by the patients.

EXAMPLE 2 In Vitro Tests

Experiments were carried out to measure the uptake of radioactivestrontium by tooth enamel from strontium-containing compositions in thepresence and absence of simultaneously applied fluoride-containingcompositions.

2.1 Toothpaste Compositions

In a first series of experiments a strontium-containing toothpastecontaining 10% by weight of SrCl₂ was used as the strontium-containingcomposition and a fluoride-containing toothpaste containing 0.76% byweight of sodium monfluorophosphate was used at the fluoride containingcomposition.

The following treatment regime was used:

1. Groups of three extracted teeth were brushed with the toothpaste(s)for 1 minute each.

2. An initial cleaning was carried out by rinsing thoroughly with tapwater.

3. The radioactivity of the teeth was measured.

4. The teeth were washed again with tap water.

5. The radioactivity of the teeth was measured again.

6. The percentage uptake of strontium was calculated and expressed as afraction of the strontium present in 100 mg of toothpaste.

A. The dependency of strontium uptake on the amount ofstrontium-containing paste was assessed by applying to each tooth either100 or 300 mg of labelled toothpaste.

The results are illustrated in FIG. 3 in which Line 1 shows the resultsof using 100 mg of toothpaste and Line 2 shows the results of using 300mg of toothpaste. It can be seen that the uptake of strontium isvirtually independent of the amount of strontium-containing toothpasteused, provided that sufficient is present to cover the tooth surface.More specifically the total uptake of labelled strontium on the toothsurface was practically the same when 100 and 300 mg of toothpaste wereused. This indicates that the uptake of strontium is presumably asurface phenomenum during the first minute of application.

B. The effect of mixing a strontium-containing toothpaste with afluoride containing toothpaste was investigated by mixing varyingamounts of the two toothpastes in situ. The results are summarised inFIG. 4 in which Line 1 shows the results of using thestrontium-containing toothpaste alone, Line 2 shows the results of using3 parts of strontium-containing toothpaste with 1 part offluoride-containing toothpaste and Line 3 shows the results of usingequal amounts of the two toothpastes.

It can be seen from FIG. 4 that by mixing the strontium and fluorideimmediately prior to application to the tooth surface there is asynergistic effect with the uptake of strontium unexpectedly beingpotentiated by the addition of fluoride.

C. Experiments were carried out to determine whether the uptake ofstrontium by tooth enamel was enhanced by a second application ofstrontium-containing toothpaste to the same teeth and what the effectwas of simultaneously applying a fluoride-containing toothpaste. Theresults are summarised in FIG. 5 in which Line 1 shows the uptake ofstrontium when using a strontium-containing toothpaste alone, Line 2shows the effect of an additional brushing with a strontium-containingtoothpaste and Line 3 shows the strontium uptake when a mixture ofstrontium toothpaste and fluoride toothpaste is used for the secondapplication. (In FIG. 5 the points 1A, 2A and 3A represent the washesafter the second application).

It can be seen that additional strontium uptake resulting from a furthertreatment with a strontium-containing toothpaste is enhanced by thepresence of fluoride (Line 3) compared to Line 2 where no fluoride isused.

2.2 Mouthwash Compositions

In a second series of experiments a liquid mouthwash composition wasprepared by instantaneous mixing 20 seconds before use of a aqueoussolution of radiactively labelled strontium (0.2% SnCl₂.6H₂ O by weight)and an aqueous solution of 0.2% NaF. The tests were carried out byequilibrating teeth with the mixture.

The results are summarised in FIG. 6 where Line 1 illustrates thepercent saturation uptake from 5 ml of the strontium chloride solutionper tooth surface and Line 2 illustrates the result of using the mixedNaF/SrO₂ solution. A significant enhancement of strontium uptakeoccurred when the mixed solution was used.

I claim:
 1. A system for preparing a desensitizing composition effectivein producing an enhanced desensitizing effect comprising strontium andfluoride, said system comprising a source of first and secondcompositions, said compositions being segregated and containingrespectively a physiologically acceptable source of free strontium ionsand a physiologically acceptable source of free fluoride ions, anddispensing means arranged to dispense said compositions so that amixture thereof may be formed on or immediately prior to applicationthereof to the teeth.
 2. A system according to claim 1 wherein saidsegregated compositions are housed in a common container and areseparated from one another by a barrier which prevents mixing prior tothe compositions being dispensed.
 3. A system according to claim 1wherein the source of strontium ion is strontium chloride.
 4. A systemaccording to claim 1 wherein the source of fluoride ion is acidulatedphosphate fluoride.
 5. A system according to claim 1 wherein each ofsaid segregated compositions is in the form of a paste or a gel.
 6. Asystem according to claim 1 wherein each of the said segregatedcompositions is in the form of a liquid solution.
 7. A system accordingto claim 1 wherein said strontium compound is present in a concentrationof between about 0.1% and about 12%.
 8. A system according to claim 1wherein the concentration of fluoride compound is between about 0.001%and about 4%.
 9. A kit for producing an enhanced desensitizing effect inthe dental area of a patient having hypersensitive teeth which comprisessupplies of two separate dentifrice or mouthwash compositions, one ofsaid compositions containing a source of a physiologically acceptablefree strontium ion and the other of said compositions containing aphysiologically acceptable source of free fluoride ion.
 10. A kitaccording to claim 9 further comprising instructions for admixing saidphases on or immediately prior to application to the teeth of thepatient to form on the surface of the teeth strontium and fluoride in aform to effect desensitization of the dental area of the patient.
 11. Amethod for obtaining an enhanced desensitizing effect in a subjectsuffering from dental sensitivity comprising providing a source of firstand second compositions, said compositions being segregated andcontaining respectively a physiologically acceptable source of freestrontium ions and a physiologically acceptable source of free fluorideions, dispensing said compositions and applying a mixture thereof to theteeth of said subject, said mixture being formed on or immediately priorto application thereof to the teeth.
 12. A method for providing anenhanced desensitizing effect in a subject suffering from dentalsensitivity, comprising:providing a dispenser having a first compartmentcontaining a first composition and a second compartment containing asecond composition, said first and second compartments being segregatedso that said first and second compositions do not intermix prior todispensing thereof, said first composition comprising a physiologicallyacceptable source of free strontium ions and said second compositioncomprising a physiologically acceptable source of free fluoride ions;and dispensing said first and second compositions onto the teeth of saidsubject and effecting mixing of said first and second compositions on orimmediately prior to application thereof to the teeth.